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The Future Is Now: Biologics for Non-Infectious Pediatric Anterior Uveitis

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Abstract

Anterior uveitis (AU), inflammation of the iris, choroid or ciliary body, can cause significant eye morbidity, including visual loss. In the pediatric age group, the most common underlying diagnosis for AU is juvenile idiopathic associated uveitis and idiopathic AU, which are the focus of this paper. AU is often resistant to medications such as topical corticosteroids and methotrexate. In the past 15 years, biologic agents (biologics) have transformed treatment. In this review, we discuss those in widespread use and those with more theoretical applications for anterior uveitis. Tumor necrosis factor alpha inhibitors (anti-TNFα) have been available the longest and are used widely to treat pediatric uveitis. The effects of anti-TNFα in children are described mostly in small retrospective case series. Together, the literature suggests that the majority of children treated with anti-TNFα achieve decreased uveitis activity and reduced corticosteroid burden. However, many will have disease flares even on treatment. Only a few small studies directly compare outcomes between alternate anti-TNFα (infliximab and adalimumab). The use of different uveitis grading systems, inclusion criteria, and outcome measures makes cross-study comparisons difficult. Whether the achievement and maintenance of inactive disease occurs more frequently with certain anti-TNFα remains controversial. Newer biologics that modulate the immune system differently (e.g., interfere with Th17 activation through IL-17a and IL-6 blockade, limit T lymphocyte costimulation, and deplete B lymphocytes), have shown promise for uveitis. Studies of these agents are small and include mostly adults. Additional biologics are also being explored to treat uveitis. With their advent, we are hopeful that outcomes will ultimately be improved for children with AU. With many biologics available, much work remains to identify the optimal inflammatory pathway to target in AU.

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References

  1. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol. 2005;140(3):509–16.

    PubMed  Google Scholar 

  2. Cunningham TE Jr. Uveitis in children. Ocul Immunol Inflamm. 2000;8(4):251–61.

    PubMed  Google Scholar 

  3. Kump LI, Cervantes-Castañeda RA, Androudi SN, Foster CS. Analysis of pediatric uveitis cases at a tertiary referral center. Ophthalmology. 2005;112(7):1287–92.

    PubMed  Google Scholar 

  4. Tugal-Tutkun I, Havrlikova K, Power WJ, Foster CS. Changing patterns in uveitis of childhood. Ophthalmology. 1996;103(3):375–83.

    CAS  PubMed  Google Scholar 

  5. Edelsten C, Reddy MA, Stanford MR, Graham EM. Visual loss associated with pediatric uveitis in english primary and referral centers. Am J Ophthalmol. 2003;135(5):676–80.

    PubMed  Google Scholar 

  6. Sabri K, Saurenmann RK, Silverman ED, Levin AV. Course, complications, and outcome of juvenile arthritis-related uveitis. J AAPOS. 2008;12(6):539–45.

    PubMed  Google Scholar 

  7. BenEzra D, Forrester JV, Nussenblatt RB, et al. Uveitis scoring system. Berlin: Springer; 1991. p. 1–9.

    Google Scholar 

  8. Foster CS, Vitale AT. Diagnosis and treatment of uveitis. Philadelphia: Saunders; 2002. p. 91–2.

    Google Scholar 

  9. Hogan MJ, Kimura SJ, Thygeson P. Signs and symptoms of uveitis. I. Anterior uveitis. Am J Ophthalmol. 1959;47:155–70.

    CAS  PubMed  Google Scholar 

  10. Nussenblatt RB, Whitcup SM. Uveitis: fundamentals and clinical practice. Philadelphia: Mosby; 2004.

    Google Scholar 

  11. Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92(4):467–71.

    CAS  PubMed  Google Scholar 

  12. Paroli MP, Spinucci G, Fabiani C, Pivetti-Pezzi P. Retinal complications of juvenile idiopathic arthritis-related uveitis: a microperimetry and optical coherence tomography study. Ocul Immunol Inflamm. 2010;18(1):54–9.

    PubMed  Google Scholar 

  13. Reiff A. Ocular complications of childhood rheumatic diseases: uveitis. Curr Rheumatol Rep. 2006;8(6):459–68.

    PubMed  Google Scholar 

  14. Darrell RW, Wagener HP, Kurland LT. Epidemiology of uveitis. Incidence and prevalence in a small urban community. Arch Ophthalmol. 1962;68:502–14.

    CAS  PubMed  Google Scholar 

  15. Päivönsalo-Hietanen T, Tuominen J, Saari KM. Uveitis in children: population-based study in Finland. Acta Ophthalmol Scand. 2000;78(1):84–8.

    PubMed  Google Scholar 

  16. Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California epidemiology of uveitis study. Ophthalmology. 2004;111(3):491–500 (discussion 500).

    PubMed  Google Scholar 

  17. Zierhut M, Michels H, Stübiger N, Besch D, Deuter C, Heiligenhaus A. Uveitis in children. Int Ophthalmol Clin. 2005;45(2):135–56.

    PubMed  Google Scholar 

  18. Heiligenhaus A, Niewerth M, Ganser G, Heinz C, Minden K. German Uveitis in Childhood Study Group. Prevalence and complications of uveitis in juvenile idiopathic arthritis in a population-based nation-wide study in Germany: suggested modification of the current screening guidelines. Rheumatology (Oxford). 2007;46(6):1015–9.

    CAS  Google Scholar 

  19. Saurenmann RK, Levin AV, Feldman BM, Laxer RM, Schneider R, Silverman ED. Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis. Arthritis Rheum. 2010;62(6):1824–8.

    CAS  PubMed  Google Scholar 

  20. Kotaniemi K, Arkela-Kautiainen M, Haapasaari J, Leirisalo-Repo M. Uveitis in young adults with juvenile idiopathic arthritis: a clinical evaluation of 123 patients. Ann Rheum Dis. 2005;64(6):871–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Angeles-Han ST, Pelajo CF, Vogler LB, Rouster-Stevens K, Kennedy C, Ponder L, et al. Risk markers of juvenile idiopathic arthritis-associated uveitis in the childhood arthritis and rheumatology research alliance (CARRA) registry. J Rheumatol. 2013;40(12):2088–96.

    PubMed Central  PubMed  Google Scholar 

  22. Ravelli A, Felici E, Magni-Manzoni S, Pistorio A, Novarini C, Bozzola E, et al. Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease. Arthritis Rheum. 2005;52(3):826–32.

    PubMed  Google Scholar 

  23. Saurenmann RK, Levin AV, Feldman BM, Rose JB, Laxer RM, Schneider R, Silverman ED. Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study. Arthritis Rheum. 2007;56(2):647–57.

    CAS  PubMed  Google Scholar 

  24. Cassidy J, Kivlin J, Lindsley C, Nocton J. Section on rheumatology, section on ophthalmology. Ophthalmologic examinations in children with juvenile rheumatoid arthritis. Pediatrics. 2006;117(5):1843–5.

    PubMed  Google Scholar 

  25. Calandra S, Gallo MC, Consolaro A, Pistorio A, Lattanzi B, Bovis F, et al. Female sex and oligoarthritis category are not risk factors for uveitis in italian children with juvenile idiopathic arthritis. J Rheumatol. 2014;41(7):1416–25.

    PubMed  Google Scholar 

  26. Chylack LT. The ocular manifestations of juvenile rheumatoid arthritis. Arthritis Rheum. 1977;20(Suppl 2):217–23.

    PubMed  Google Scholar 

  27. Holland GN, Stiehm E. Special considerations in the evaluation and management of uveitis in children. Am J Ophthalmol. 2003;135(6):867–78.

    PubMed  Google Scholar 

  28. Woreta F, Thorne JE, Jabs DA, Kedhar SR, Dunn JP. Risk factors for ocular complications and poor visual acuity at presentation among patients with uveitis associated with juvenile idiopathic arthritis. Am J Ophthalmol. 2007;143(4):647–55.

    PubMed Central  PubMed  Google Scholar 

  29. Zulian F, Martini G, Falcini F, Gerloni V, Zannin ME, Pinello L, et al. Early predictors of severe course of uveitis in oligoarticular juvenile idiopathic arthritis. J Rheumatol. 2002;29(11):2446–53.

    PubMed  Google Scholar 

  30. Edelsten C, Lee V, Bentley CR, Kanski JJ, Graham EM. An evaluation of baseline risk factors predicting severity in juvenile idiopathic arthritis associated uveitis and other chronic anterior uveitis in early childhood. Br J Ophthalmol. 2002;86(1):51.

    PubMed Central  PubMed  Google Scholar 

  31. Thorne JE, Woreta F, Kedhar SR, Dunn JP, Jabs DA. Juvenile idiopathic arthritis-associated uveitis: incidence of ocular complications and visual acuity loss. Am J Ophthalmol. 2007;143(5):840–6.

    PubMed  Google Scholar 

  32. Holland GN. A reconsideration of anterior chamber flare and its clinical relevance for children with chronic anterior uveitis (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2007;105:344–64.

    PubMed Central  PubMed  Google Scholar 

  33. Zannin ME, Buscain I, Vittadello F, Martini G, Alessio M, Orsoni JG, et al. Timing of uveitis onset in oligoarticular juvenile idiopathic arthritis (JIA) is the main predictor of severe course uveitis. Acta Ophthalmol. 2012;90(1):91–5.

    CAS  PubMed  Google Scholar 

  34. Angeles-Han S, Yeh S. Prevention and management of cataracts in children with juvenile idiopathic arthritis-associated uveitis. Curr Rheumatol Rep. 2012;14(2):142–9.

    PubMed Central  PubMed  Google Scholar 

  35. Thorne JE, Woreta FA, Dunn JP, Jabs DA. Risk of cataract development among children with juvenile idiopathic arthritis-related uveitis treated with topical corticosteroids. Ophthalmology. 2010;117(7):1436–41.

    PubMed Central  PubMed  Google Scholar 

  36. Kazdan JJ, McCulloch JC, Crawford JS. Uveitis in children. Can Med Assoc J. 1967;96(7):385.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Heiligenhaus A, Michels H, Schumacher C, Kopp I, Neudorf U, Niehues T, et al. Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Rheumatol Int. 2012;32(5):1121–33.

    CAS  PubMed  Google Scholar 

  38. Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130(4):492–513.

    CAS  PubMed  Google Scholar 

  39. Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol. 2005;32(2):362–5.

    CAS  PubMed  Google Scholar 

  40. Gangaputra S, Newcomb CW, Liesegang TL, Kaçmaz RO, Jabs DA, Levy-Clarke GA, et al. Methotrexate for ocular inflammatory diseases. Ophthalmology. 2009;116(11):2188–98.e1.

  41. Heiligenhaus A, Mingels A, Heinz C, Ganser G. Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti-inflammatory medication. Eur J Ophthalmol. 2007;17(5):743–8.

    CAS  PubMed  Google Scholar 

  42. Malik AR, Pavesio C. The use of low dose methotrexate in children with chronic anterior and intermediate uveitis. Br J Ophthalmol. 2005;89(7):806–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Samson CM, Waheed N, Baltatzis S, Foster CS. Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients. Ophthalmology. 2001;108(6):1134–9.

    CAS  PubMed  Google Scholar 

  44. Weiss AW, Wallace CW, Sherry DS. Methotrexate for resistant chronic uveitis in children with juvenile rheumatoid arthritis. J Pediatr. 1998;133(133):266–8.

    CAS  PubMed  Google Scholar 

  45. Doycheva D, Deuter C, Stuebiger N, Biester S, Zierhut M. Mycophenolate mofetil in the treatment of uveitis in children. Br J Ophthalmol. 2007;91(2):180–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Goebel JC, Roesel M, Heinz C, Michels H, Ganser G, Heiligenhaus A. Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis. Br J Ophthalmol. 2011;95(2):209–13.

    CAS  PubMed  Google Scholar 

  47. Daniel E, Thorne JE, Newcomb CW, Pujari SS, Kaçmaz RO, Levy-Clarke GA, et al. Mycophenolate mofetil for ocular inflammation. Am J Ophthalmol. 2010;149(3):423–32.e1-2.

  48. Molina C, Modesto C, Martín-Begué N, Arnal C. Leflunomide, a valid and safe drug for the treatment of chronic anterior uveitis associated with juvenile idiopathic arthritis. Clin Rheumatol. 2013;32(11):1673–5.

    PubMed  Google Scholar 

  49. BenEzra D, Cohen E, Rakotomalala M, de Courten C, Harris W, Chajek T, Friedman G, Matamoros N. Treatment of endogenous uveitis with cyclosporine A. Transplant Proc. 1988;20(3 Suppl 4):122–7.

    CAS  PubMed  Google Scholar 

  50. Kaçmaz RO, Kempen JH, Newcomb C, Daniel E, Gangaputra S, Nussenblatt RB, et al. Cyclosporine for ocular inflammatory diseases. Ophthalmology. 2010;117(3):576–84.

    PubMed Central  PubMed  Google Scholar 

  51. Kalinina Ayuso V, van de Winkel EL, Rothova A, DeBoer JH. Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis. Am J Ophthalmol. 2011;151(2):217–22.

    PubMed  Google Scholar 

  52. Simonini G, Paudyal P, Jones GT, Cimaz R, Macfarlane GJ. Current evidence of methotrexate efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach. Rheumatology (Oxford). 2013;52(5):825–31.

    CAS  Google Scholar 

  53. Aggarwal BB, Gupta SC, Kim JH. Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood. 2012;119(3):651–65.

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Nie H, Zheng Y, Li R, Guo TB, He D, Fang L, et al. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by tnf-α in rheumatoid arthritis. Nat Med. 2013;19(3):322–8.

    CAS  PubMed  Google Scholar 

  55. Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, Dewitt EM, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken). 2011;63(4):465–82.

    Google Scholar 

  56. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625–39.

    CAS  Google Scholar 

  57. Dick AD, Forrester JV, Liversidge J, Cope AP. The role of tumour necrosis factor (TNF-alpha) in experimental autoimmune uveoretinitis (EAU). Prog Retin Eye Res. 2004;23(6):617–37.

    CAS  PubMed  Google Scholar 

  58. Santos Lacomba M, Marcos Martin C, Gallardo Galera JMA, Vidal G, Collantes Estevez E, Ramirez Chamond R, Omar MM. Aqueous humor and serum tumor necrosis factor-α in clinical uveitis. Ophthalmic Res. 2001;33(5):251–5.

    CAS  PubMed  Google Scholar 

  59. Reiff A, Takei S, Sadeghi S, Stout A, Shaham B, Bernstein B, et al. Etanercept therapy in children with treatment-resistant uveitis. Arthritis Rheum. 2001;44(6):1411–5.

    CAS  PubMed  Google Scholar 

  60. Smith JR, Levinson RD, Holland GN, Jabs DA, Robinson MR, Whitcup SM, Rosenbaum JT. Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic disease. Arthritis Rheum. 2001;45(3):252–7.

    CAS  PubMed  Google Scholar 

  61. Saurenmann RK, Levin AV, Feldman BM, Laxer RM, Schneider R, Silverman ED. Risk of new-onset uveitis in patients with juvenile idiopathic arthritis treated with anti-tnfalpha agents. J Pediatr. 2006;149(6):833–6.

    CAS  PubMed  Google Scholar 

  62. Smith JA, Thompson DJ, Whitcup SM, Suhler E, Clarke G, Smith S, et al. A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis Rheum. 2005;53(1):18–23.

    CAS  PubMed  Google Scholar 

  63. Richards JC, Tay-Kearney ML, Murray K, Manners P. Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Experiment Ophthalmol. 2005;33(5):461–8.

    PubMed  Google Scholar 

  64. Rajaraman RT, Kimura Y, Li S, Haines K, Chu DS. Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology. 2006;113(2):308–14.

    PubMed  Google Scholar 

  65. Kahn P, Weiss M, Imundo LF, Levy DM. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology. 2006;113(5):860–4.e2.

  66. Sobrin L, Kim EC, Christen W, Papadaki T, Letko E, Foster CS. Infliximab therapy for the treatment of refractory ocular inflammatory disease. Arch Ophthalmol. 2007;125(7):895.

    CAS  PubMed  Google Scholar 

  67. Ardoin SP, Kredich D, Rabinovich E, Schanberg LE, Jaffe GJ. Infliximab to treat chronic noninfectious uveitis in children: retrospective case series with long-term follow-up. Am J Ophthalmol. 2007;144(6):844–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Tugal-Tutkun I, Ayranci O, Kasapcopur O, Kir N. Retrospective analysis of children with uveitis treated with infliximab. J AAPOS. 2008;12(6):611–3.

    PubMed  Google Scholar 

  69. Sharma SM, Ramanan AV, Riley P, Dick AD. Use of infliximab in juvenile onset rheumatological disease associated refractory uveitis: efficacy in joint and ocular disease. Ann Rheum Dis. 2007;66:840–1.

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Simonini G, Zannin ME, Caputo R, Falcini F, de Martino M, Zulian F, Cimaz R. Loss of efficacy during long-term infliximab therapy for sight-threatening childhood uveitis. Rheumatology (Oxford). 2008;47(10):1510–4.

    CAS  Google Scholar 

  71. Ducourau E, Mulleman D, Paintaud G, Miow Lin DC, Lauféron F, Ternant D, et al. Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases. Arthritis Res Ther. 2011;13(3):R105.

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease. Gastroenterology. 2004;126(2):402–13.

    CAS  PubMed  Google Scholar 

  73. Wolbink GJ, Vis M, Lems W, Voskuyl AE, de Groot E, Nurmohamed MT, et al. Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54(3):711–5.

    PubMed  Google Scholar 

  74. Vazquez-Cobian LB, Flynn T, Lehman TJA. Adalimumab therapy for childhood uveitis. J Pediatr. 2006;149(4):572–5.

    CAS  PubMed  Google Scholar 

  75. Kempen JH, Ganesh SK, Sangwan VS, Rathinam SR. Interobserver agreement in grading activity and site of inflammation in eyes of patients with uveitis. Am J Ophthalmol. 2008;146(6):813–8.e1.

  76. Biester S, Deuter C, Michels H, Haefner R, Kuemmerle-Deschner J, Doycheva D, Zierhut M. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol. 2007;91(3):319–24.

    PubMed Central  PubMed  Google Scholar 

  77. Bravo-Ljubetic L, Peralta-Calvo J, Noval S, Pastora-Salvador N, Abelairas-Gómez J, Merino R. Adalimumab therapy for refractory childhood uveitis. J AAPOS. 2013;17(5):456–9.

    PubMed  Google Scholar 

  78. Gallagher M, Quinones K, Cervantes-Castaneda RA, Yilmaz T, Foster CS. Biological response modifier therapy for refractory childhood uveitis. Br J Ophthlamol. 2007;91(10):1341.

    Google Scholar 

  79. Tynjälä P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, Lahdenne P. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology (Oxford). 2008;47(3):339–44.

    Google Scholar 

  80. Kotaniemi K, Säilä H, Kautiainen H. Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis. Clin Ophthalmol. 2011;5:1425–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Sen ES, Sharma S, Hinchcliffe A, Dick AD, Ramanan AV. Use of adalimumab in refractory non-infectious childhood chronic uveitis: efficacy in ocular disease—a case cohort interventional study. Rheumatology (Oxford). 2012;51(12):2199–203.

    CAS  PubMed  Google Scholar 

  82. Doycheva D, Zierhut M, Blumenstock G, Stuebiger N, Januschowski K, Voykov B, Deuter C. Immunomodulatory therapy with tumour necrosis factor α inhibitors in children with antinuclear antibody-associated chronic anterior uveitis: long-term results. Br J Ophthalmol. 2014;98(4):523–8.

    PubMed  Google Scholar 

  83. Saurenmann RK, Levin AV, Rose JB, Parker S, Rabinovitch T, Tyrrell PN, et al. Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology (Oxford). 2006;45(8):982–9.

    CAS  Google Scholar 

  84. Simonini G, Druce K, Cimaz R, Macfarlane GJ, Jones GT. Current evidence of anti-tumor necrosis factor α treatment efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach of individual drugs. Arthritis Care Res (Hoboken). 2014;66(7):1073–84.

    CAS  Google Scholar 

  85. Zannin ME, Birolo C, Gerloni VM, Miserocchi E, Pontikaki I, Paroli MP, et al. Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis: 1-year followup data from the Italian registry. J Rheumatol. 2013;40(1):74–9.

    CAS  PubMed  Google Scholar 

  86. Simonini G, Taddio A, Cattalini M, Caputo R, De Libero C, Naviglio S, et al. Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res (Hoboken). 2011;63(4):612–8.

    CAS  Google Scholar 

  87. Sukumaran S, Marzan K, Shaham B, Reiff A. High dose infliximab in the treatment of refractory uveitis: does dose matter? ISRN Rheumatol. 2012;2012:765380.

    PubMed Central  PubMed  Google Scholar 

  88. Ruperto N, Lovell DJ, Cuttica R, Wilkinson N, Woo P, Espada G, et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007;56(9):3096–106.

    CAS  PubMed  Google Scholar 

  89. Aeschlimann FA, Hofer KD, Cannizzaro Schneider E, Schroeder S, Lauener R, Saurenmann RK. Infliximab in pediatric rheumatology patients: a retrospective analysis of infusion reactions and severe adverse events during 2246 infusions over 12 years. J Rheumatol. 2014;41(7):1409–15.

    CAS  PubMed  Google Scholar 

  90. Tambralli A, Beukelman T, Weiser P, Atkinson TP, Cron RQ, Stoll ML. High doses of infliximab in the management of juvenile idiopathic arthritis. J Rheumatol. 2013;40(10):1749–55.

    CAS  PubMed  Google Scholar 

  91. Dhingra N, Morgan J, Dick AD. Switching biologic agents for uveitis. Eye (Lond). 2009;23(9):1868–70.

    CAS  Google Scholar 

  92. Simonini G, Katie D, Cimaz R, Macfarlane GJ, Jones GT. Does switching anti-tnfα biologic agents represent an effective option in childhood chronic uveitis: the evidence from a systematic review and meta-analysis approach. Semin Arthritis Rheum. 2014;44(1):39–46.

    CAS  PubMed  Google Scholar 

  93. Lerman MA, Burnham JM, Chang PY, Daniel E, Foster CS, Hennessy S, et al. Response of pediatric uveitis to tumor necrosis factor-α inhibitors. J Rheumatol. 2013;40(8):1394–403.

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295(19):2275–85.

    CAS  PubMed  Google Scholar 

  95. Costenbader KH, Glass R, Cui J, Shadick N. Risk of serious infections and malignancies with anti-TNF antibody therapy in rheumatoid arthritis. JAMA. 2006;296(18):2201.

    CAS  PubMed  Google Scholar 

  96. Diak P, Siegel J, La Grenade L, Choi L, Lemery S, McMahon A. Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the food and drug administration. Arthritis Rheum. 2010;62(8):2517–24.

    PubMed  Google Scholar 

  97. Askling J, van Vollenhoven RF, Granath F, Raaschou P, Fored CM, Baecklund E, et al. Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: does the risk change with the time since start of treatment? Arthritis Rheum. 2009;60(11):3180–9.

    CAS  PubMed  Google Scholar 

  98. Beukelman T, Haynes K, Curtis JR, Xie F, Chen L, Bemrich-Stolz CJ, et al. Rates of malignancy associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum. 2012;64(4):1263–71.

    PubMed Central  PubMed  Google Scholar 

  99. Simard JF, Neovius M, Hagelberg S, Askling J. Juvenile idiopathic arthritis and risk of cancer: a nationwide cohort study. Arthritis Rheum. 2010;62(12):3776–82.

    CAS  PubMed  Google Scholar 

  100. Schneeweiss S, Korzenik J, Solomon DH, Canning C, Lee J, Bressler B. Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections. Aliment Pharmacol Ther. 2009;30(3):253–64.

    CAS  PubMed  Google Scholar 

  101. Beukelman T, Xie F, Chen L, Baddley JW, Delzell E, Grijalva CG, et al. Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum. 2012;64(8):2773–80.

    PubMed Central  PubMed  Google Scholar 

  102. Heiligenhaus A, Foeldvari I, Edelsten C, Smith JR, Saurenmann RK, Bodaghi B, et al. Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis: a consensus effort from the multinational interdisciplinary working group for uveitis in childhood. Arthritis Care Res (Hoboken). 2012;64(9):1365–72.

    Google Scholar 

  103. Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, et al. TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med. 2007;13(6):711–8.

    CAS  PubMed  Google Scholar 

  104. Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, et al. Effects of AIN457, a fully human antibody to interleukin-17a, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010;2(52):52ra72.

    PubMed  Google Scholar 

  105. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371(4):326–38.

    PubMed  Google Scholar 

  106. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235–8.

    CAS  PubMed  Google Scholar 

  107. Mima T, Nishimoto N. Clinical value of blocking IL-6 receptor. Curr Opin Rheumatol. 2009;21(3):224–30.

    CAS  PubMed  Google Scholar 

  108. Calvo-Río V, de la Hera D, Beltrán-Catalán E, Blanco R, Hernandez M, Martínez-Costa L, et al. Tocilizumab in uveitis refractory to other biologic drugs: a study of 3 cases and a literature review. Clin Exp Rheumatol. 2014;32(4 Suppl 84):S54–7.

    PubMed  Google Scholar 

  109. Muselier A, Bielefeld P, Bidot S, Vinit J, Besancenot JF, Bron A. Efficacy of tocilizumab in two patients with anti-tnf-alpha refractory uveitis. Ocul Immunol Inflamm. 2011;19(5):382–3.

    CAS  PubMed  Google Scholar 

  110. Tappeiner C, Heinz C, Ganser G, Heiligenhaus A. Is tocilizumab an effective option for treatment of refractory uveitis associated with juvenile idiopathic arthritis? J Rheumatol. 2012;39(6):1294–5.

    PubMed  Google Scholar 

  111. Tsang AC, Roth J, Gottlieb C. Tocilizumab for severe chronic anterior uveitis associated with juvenile idiopathic arthritis in a pediatric patient. Ocul Immunol Inflam. 2013;22(2):155–7.

    Google Scholar 

  112. Planck SR, Woods A, Clowers JS, Nicklin MJ, Rosenbaum JT, Rosenzweig HL. Impact of IL-1 signalling on experimental uveitis and arthritis. Ann Rheum Dis. 2012;71(5):753–60.

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Simonini G, Xu Z, Caputo R, De Libero C, Pagnini I, Pascual V, Cimaz R. Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in blau syndrome-related uveitis. Arthritis Rheum. 2013;65(2):513–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Ugurlu S, Ucar D, Seyahi E, Hatemi G, Yurdakul S. Canakinumab in a patient with juvenile Behcet’s syndrome with refractory eye disease. Ann Rheum Dis. 2012;71(9):1589–91.

    PubMed  Google Scholar 

  115. Wroblewski K, Sen HN, Yeh S, Faia L, Li Z, Sran P, et al. Long-term daclizumab therapy for the treatment of noninfectious ocular inflammatory disease. Can J Ophthalmol. 2011;46(4):322–8.

    PubMed Central  PubMed  Google Scholar 

  116. Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Pérez N, Silva CA, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372(9636):383–91.

    CAS  PubMed  Google Scholar 

  117. Angeles-Han S, Flynn T, Lehman T. Abatacept for refractory juvenile idiopathic arthritis-associated uveitis—a case report. J Rheumatol. 2008;35(9):1897–8.

    PubMed  Google Scholar 

  118. Zulian F, Balzarin M, Falcini F, Martini G, Alessio M, Cimaz R, et al. Abatacept for severe anti-tumor necrosis factor alpha refractory juvenile idiopathic arthritis-related uveitis. Arthritis Care Res (Hoboken). 2010;62(6):821–5.

    CAS  Google Scholar 

  119. Elhai M, Deslandre CJ, Kahan A. Abatacept for refractory juvenile idiopathic arthritis-associated uveitis: two new cases. Comment on the article by Zulian et al. Arthritis Care Res (Hoboken). 2011;63(2):307–8.

    Google Scholar 

  120. Kenawy N, Cleary G, Mewar D, Beare N, Chandna A, Pearce I. Abatacept: a potential therapy in refractory cases of juvenile idiopathic arthritis-associated uveitis. Graefes Arch Clin Exp Ophthalmol. 2011;249(2):297–300.

    PubMed  Google Scholar 

  121. Silver PB, Hathcock KS, Chan CC, Wiggert B, Caspi RR. Blockade of costimulation through B7/CD28 inhibits experimental autoimmune uveoretinitis, but does not induce long-term tolerance. J Immunol. 2000;165(9):5041–7.

    CAS  PubMed  Google Scholar 

  122. Miserocchi E, Pontikaki I, Modorati G, Gattinara M, Meroni PL, Gerloni V. Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases. Autoimmun Rev. 2011;11(1):35–9.

    CAS  PubMed  Google Scholar 

  123. Pelegrin L, Jakob E, Schmidt-Bacher A, Schwenger V, Becker M, Max R, et al. Experiences with rituximab for the treatment of autoimmune diseases with ocular involvement. J Rheumatol. 2014;41(1):84–90.

    CAS  PubMed  Google Scholar 

  124. Heiligenhaus A, Miserocchi E, Heinz C, Gerloni V, Kotaniemi K. Treatment of severe uveitis associated with juvenile idiopathic arthritis with anti-cd20 monoclonal antibody (rituximab). Rheumatology (Oxford). 2011;50(8):1390–4.

    CAS  Google Scholar 

  125. Commodaro AG, Peron JP, Lopes CT, Arslanian C, Belfort R, Rizzo LV, Bueno V. Evaluation of experimental autoimmune uveitis in mice treated with FTY720. Invest Ophthalmol Vis Sci. 2010;51(5):2568–74.

    PubMed  Google Scholar 

  126. Stevenson W, Sadrai Z, Hua J, Kodati S, Huang JF, Chauhan SK, Dana R. Effects of topical janus kinase inhibition on ocular surface inflammation and immunity. Cornea. 2014;33(2):177–83.

    PubMed  Google Scholar 

  127. Xiang Q, Chen L, Fang J, Hou S, Wei L, Bai L, et al. TNF receptor-associated factor 5 gene confers genetic predisposition to acute anterior uveitis and pediatric uveitis. Arthritis Res Ther. 2013;15(5):R113.

    PubMed Central  PubMed  Google Scholar 

  128. Reiff A. Long-term outcome of etanercept therapy in children with treatment-refractory uveitis. Arthritis Rheum. 2003;48(7):2079–80.

    PubMed  Google Scholar 

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Acknowledgments

MA Lerman and CE Rabinovich declare no conflicts of interest. No sources of funding were used to support the writing of this manuscript.

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  1. Division of Rheumatology, The Children’s Hospital of Philadelphia (CHOP), Abramson Research Center Suite 1102, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Melissa A. Lerman

  2. Division of Pediatric Rheumatology, Duke University, Durham, NC, USA

    C. Egla Rabinovich

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Correspondence to Melissa A. Lerman.

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Lerman, M.A., Rabinovich, C.E. The Future Is Now: Biologics for Non-Infectious Pediatric Anterior Uveitis. Pediatr Drugs 17, 283–301 (2015). https://doi.org/10.1007/s40272-015-0128-2

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